Apoptotic Effect of Astragalin in Melanoma Skin Cancers via Activation of Caspases and Inhibition of Sry-related HMg-Box Gene 10

Phytother Res. 2017 Oct;31(10):1614-1620. doi: 10.1002/ptr.5895. Epub 2017 Aug 15.


Though Astragalin (kaempferol-3-glucoside) contained in Paeonia lactiflora and other plants was known to have anti-oxidant, antiinflammatory, and anti-tumor activity, the anti-tumor mechanism of Astragalin has never been reported in melanomas until now. Thus, in the present study, the underlying apoptotic mechanism of Astragalin isolated from Aceriphyllum rossii was elucidated in A375P and SK-MEL-2 melanoma cells. Astragalin exerted cytotoxicity in A375P and SK-MEL-2 cells in a concentration-dependent manner. Also, Astragalin significantly increased the number of TdT-mediated dUTP nick end labeling positive cells and sub-G1 population as a feature of apoptosis in A375P and SK-MEL-2 cells compared with untreated control. Consistently, western blotting revealed that Astragalin activated caspase 9/3 and Bax, cleaved poly (ADP-ribose) polymerase, and attenuated the expression of cyclin D1, Mcl-1, and Sry-related HMg-Box gene 10 (SOX10) in A375P and SK-MEL-2 cells. Of note, ectopic expression of SOX10 reduced the apoptotic ability of Astragalin to inhibit proliferation, cleave poly (ADP-ribose) polymerase, and caspase 3 in A375P and SK-MEL-2 melanoma cells. Overall, our findings provide evidence that Astragalin induces apoptosis in A375P and SK-MEL-2 melanoma cells via activation of caspase9/3 and inhibition of SOX10 signaling. Copyright © 2017 John Wiley & Sons, Ltd.

Keywords: Astragalin; PARP; SOX10; TUNEL; apoptosis; melanoma.

MeSH terms

  • Apoptosis*
  • Caspase 3 / metabolism*
  • Caspase 9 / metabolism*
  • Cell Line, Tumor
  • Cyclin D1 / metabolism
  • Humans
  • Kaempferols / pharmacology*
  • Melanoma / drug therapy
  • Melanoma / metabolism*
  • Myeloid Cell Leukemia Sequence 1 Protein / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • SOXE Transcription Factors / metabolism*
  • Signal Transduction / drug effects
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / metabolism*
  • bcl-2-Associated X Protein / metabolism


  • BAX protein, human
  • CCND1 protein, human
  • Kaempferols
  • MCL1 protein, human
  • Myeloid Cell Leukemia Sequence 1 Protein
  • SOX10 protein, human
  • SOXE Transcription Factors
  • bcl-2-Associated X Protein
  • Cyclin D1
  • astragalin
  • Poly(ADP-ribose) Polymerases
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9